Board Review Acid Base Disorders 722013 Metabolic Acidosis

Board Review Acid Base Disorders 7/2/2013

Metabolic Acidosis • Anion Gap Acidosis = decrease in bicarbonate due to presence of unmeasured acid (lactate) • Non-Anion Gap Acidosis = lack of bicarbonate in which chloride increases to maintain neutrality (Diarrhea)

Metabolic Acidosis • Mixed Picture – Calculate corrected bicarbonate Corrected Bicarbonate = 24 – Δ Anion Gap Measured > Corrected = Metabolic Alkalosis Measured < Corrected = Normal Anion Gap Acidosis

Anion Gap Metabolic Acidosis • Examples: – Lactic Acidosis, DKA, Alcoholic Ketoacidosis, Ethylene Glycol Toxicity, Methanol Toxicity, Proylene Glycol Toxicity, Salicylate Toxicity

Anion Gap Metabolic Acidosis • Propofol-Related Infusion Syndrome – IV dosing > 4 mg/kg/h for more than 48 hours can induce lactic acidosis – Also leads to rhabdomyolysis, hyperlipidemia, and Jpoint elevation on EKG • D-Lactic Acidosis – Occurs in short bowel syndrome after bowel resection; secondary to carbohydrate conversion to Dlactate by flora in the colon – Symptoms include: confusion, slurred speech, and ataxia

Non-Anion Gap Metabolic Acidosis • Use the Urine Anion Gap – AG = Na + K – Cl • AG Negative = presence of ammonium and appropriate kidney response to metabolic acidosis (Diarrhea) • AG Positive = no ammonium and inadequate kidney response to acidosis (RTA)

Type I RTA • Impaired excretion of hydrogen ions • Leads to urine p. H > 6. 0 and nephrocalcinosis

Type II RTA • Reduction of bicarbonate reabsorption • Bicarbonate eventually becomes reabsorbed once serum level falls low enough • Urine eventually becomes devoid of bicarbonate and p. H becomes < 5. 5 (chronically)

Type IV RTA • Usually associated with hypoaldosteronism • Hyperkalemia • Urine p. H < 5. 5

Metabolic Alkalosis • Saline Responsive with decreased ECF and intravascular volume (Vomiting, Diuretic use) – Use normal saline • Saline Responsive with Increased ECF and decreased intravascular volume (CHF, Cirrhosis) – Use acetazolamide (blocks carbonic anhydrase leading to blocked secretion of hydrogen ions and increased excretion of bicarbonate)

A 56 -year-old man is evaluated in the emergency department after his wife found him unconscious. She reports that he has a history of alcohol abuse. He is treated with lorazepam, thiamine and 1 L of D 5/NS. Upon arrival, he has a generalized seizure that resolves spontaneously. Which of the following is the most appropriate next step in management? A Fomepizole B Hemodialysis C Sodium bicarbonate D Supportive care Laboratory studies: Initial 30 Minutes Later Blood urea nitrogen 56 mg/d. L (20 mmol/L) 42 mg/d. L (15 mmol/L) Serum creatinine 1. 6 mg/d. L (141 µmol/L) 1. 5 mg/d. L (133 µmol/L) Sodium 133 meq/L (133 mmol/L) 135 meq/L (135 mmol/L) Potassium 3. 5 meq/L (3. 5 mmol/L) 3. 4 meq/L (3. 4 mmol/L) Chloride 92 meq/L (92 mmol/L) 97 meq/L (97 mmol/L) Bicarbonate 16 meq/L (16 mmol/L) 20 meq/L (20 mmol/L) Ethanol 88 mg/d. L (19 mmol/L) - Glucose 90 mg/d. L (5. 0 mmol/L) 102 mg/d. L (5. 7 mmol/L) Osmolality 320 mosm/kg H 2 O - p. H 7. 15 7. 30 PCO 2 40 mm Hg (5. 3 k. Pa) 37 mm Hg (4. 9 k. Pa) PO 2 86 mm Hg (11. 4 k. Pa) Urinalysis p. H 5. 4; trace protein; 1+ ketones; few hyaline casts Electrolytes Arterial blood gas studies (ambient air): 92 mm Hg (12. 2 k. Pa)

• AG acidosis with respiratory acidosis (normal PCO 2 in setting of acidosis) • Seizure related lactic acidosis with alcoholic ketoacidosis • Respiratory Acidosis secondary to postictal state • Improves with volume repletion and supplemental glucose

• No osmolal gap when you add ethanol – 320 -314 = 6 (no gap) – No indication for fomepizole if no osmolar gap (methanol or ethylene glycol ingestion) • HD not indicated as no toxic ingestion is suspected • Sodium bicarb used only to keep p. H > 7. 15

A 42 -year-old man hospitalized for recurrent variceal bleeding is evaluated for severe metabolic alkalosis. He has a 4 -year history of alcoholic cirrhosis. He required six units of packed red blood cells and four units of fresh frozen platelets to maintain hemodynamic stability. On physical examination, temperature is normal, BP is 100/70 mm Hg, and HR is 96/min. Cardiopulmonary examination is normal. Ascites is noted. There is 2+ presacral edema and 2+ leg edema. Laboratory studies: Serum creatinine Hospital Day 2 1. 2 mg/d. L (106 µmol/L) - Electrolytes Sodium 138 meq/L (138 136 meq/L (136 mmol/L) Potassium 3. 8 meq/L (3. 8 mmol/L) Chloride 105 meq/L (105 85 meq/L (85 mmol/L) Bicarbonate 21 meq/L (21 mmol/L) 38 meq/L (38 mmol/L) - <5 meq/L (5 mmol/L) (normal range for men, 25 -371 meq/L [25 -371 mmol/L]) p. H - 7. 52 PCO 2 - Which of the following is the most appropriate management? A Add acetazolamide On Admission Urine chloride B Add furosemide C Add isotonic saline D Discontinue octreotide 5. 0 meq/L (5. 0 mmol/L) Arterial blood gas studies (ambient air): 48 mm Hg (6. 4

• Metabolic alkalosis from metabolism of citrate in blood products (increase bicarbonate) • Impaired excretion of bicarbonate due to poor renal perfusion from cirrhosis because of increased proximal reabsoprtion of bicarbonate • Acetazolamide will improve both alkalosis and volume retention

• Furosemide facilitates sodium chloride excretion, not bicarbonate excretion • Saline would worsen fluid status as patient has increased ECF

A 23 -year-old woman is evaluated in the emergency department for a 2 -month history of progressive leg weakness. She reports no diarrhea or weight loss. Medical history is remarkable for Sjögren syndrome. She takes no medications. On physical examination, vital signs are normal. Diffuse weakness is noted most prominently in the legs, graded at 3/5. Laboratory studies: Albumin 4. 5 g/d. L (45 g/L) Blood urea nitrogen 13 mg/d. L (4. 6 mmol/L) Calcium 9. 1 mg/d. L (2. 3 mmol/L) Serum creatinine 1. 1 mg/d. L (97. 2 µmol/L) Electrolytes Sodium 141 meq/L (141 mmol/L) Potassium 1. 9 meq/L (1. 9 mmol/L) Which of the following is the most likely diagnosis? Chloride 117 meq/L (117 mmol/L) Bicarbonate 14 meq/L (14 mmol/L) A Gitelman syndrome Magnesium 2. 2 mg/d. L (0. 91 mmol/L) Phosphorus 3. 5 mg/d. L (1. 13 mmol/L) Total protein 8. 9 g/d. L (89 g/L) Urine anion gap Positive Urinalysis Specific gravity 1. 014; p. H 7. 0; no blood; trace protein; no glucose; no leukocyte esterase; no nitrites B Distal (type 1) renal tubular acidosis C Laxative abuse D Proximal (type 2) renal tubular acidosis

• • Normal AG and hypokalemia Inability to secret hydrogen ions = p. H > 6. 0 Calcinosis Positive urine AG (no ammonium in the urine)

• Gitelman syndrome leads to metabolic alkalosis and is associated with hypomagnesemia • Laxative abuse would have a negative urinary AG (appropriate kidney response to acidosis) • RTA Type II has urine p. H < 5. 5 (bicarbonate is eventually reabsorbed once serum level has fallen enough)

Laboratory studies: An 18 -year-old woman is evaluated for a 6 month history of progressive weakness and a 11 -Blood urea nitrogen lb weight loss. She reports increased fatigue and Serum creatinine Electrolytes myalgia following exercise during the past 2 Sodium months. Potassium On physical examination, the patient is thin. Temperature is 97. 6 °F, BP is 110/60 mm Hg, HR Chloride Bicarbonate is 96/min. BMI is 18. The remainder of the Urine studies: examination is unremarkable. Creatinine Which of the following is the most likely cause of this patient's acid-base disorder? Sodium Potassium A Diuretic abuse B Distal (type 1) renal tubular acidosis Chloride 4 mg/d. L (1. 4 mmol/L) 0. 5 mg/d. L (44. 2 µmol/L) 135 meq/L (135 mmol/L) 3. 1 meq/L (3. 1 mmol/L) 108 meq/L (108 mmol/L) 18 meq/L (18 mmol/L) 120 mg/d. L (normal range for women, 15 -327 mg/d. L) 22 meq/L (22 mmol/L) (normal range for women, 15 -267 meq/L [15 -267 mmol/L]) 15 meq/L (15 mmol/L) (normal range for women, 17 -164 meq/L [17 -164 mmol/L]) 45 meq/L (45 mmol/L) (normal range for women, 20 -295 meq/L [20 -295 mmol/L]) Urea 112 mg/d. L (normal range for women, 132 -1629 mg/d. L) Osmolality 290 mosm/kg H 2 O (normal range, 300 -900 mosm/kg H 2 O) Urinalysis Specific gravity 1. 012; p. H 5. 8; no blood, protein, glucose, leukocyte esterase, ketones, or nitrites C Laxative abuse D Surreptitious vomiting

• Normal anion gap metabolic acidosis • Urine anion gap is negative ( 22 + 15 – 45) = -8 • Bicarbonate loss exceeds increased ammonium excretion

• Diuretic abuse and vomiting leads to metabolic alkalosis • RTA Type I would expect a positive urine anion gap

A 42 -year-old man is evaluated in the emergency department for increased confusion. He has psoriasis and was treated with cream and a body wrap for 1 hour. He subsequently developed nausea and vomiting. He reports hearing water in his ears. He also has hypertension and type 2 diabetes mellitus complicated by proteinuria. Medications are enalapril and metformin. On physical examination, the patient is irritable, anxious, and intermittently somnolent but easily aroused. Temperature is 99. 7 °F, BP is 160/100 mm Hg, HR is 106/min standing, and RR is 20/min. Which of the following is the most likely cause of this patient's clinical presentation? A Metformin toxicity B Methanol toxicity Laboratory studies: Hemoglobin 14. 4 g/d. L (144 g/L) Leukocyte count 6300/µL (6. 3 × 10 9/L) Blood urea nitrogen 15 mg/d. L (5. 4 mmol/L) Serum creatinine 1. 3 mg/d. L (115 µmol/L) Electrolytes Sodium 145 meq/L (145 mmol/L) Potassium 3. 6 meq/L (3. 6 mmol/L) Chloride 109 meq/L (109 mmol/L) Bicarbonate 18 meq/L (22 mmol/L) Glucose 158 mg/d. L (8. 8 mmol/L) Lactic acid 7. 2 mg/d. L (0. 8 mmol/L) Osmolality 308 mosm/kg H 2 O Arterial blood gas studies (ambient air): p. H 7. 51 PCO 2 35 mm Hg (4. 7 k. Pa) PO 2 96 mm Hg (12. 8 k. Pa) Urinalysis Specific gravity 1. 024; p. H 6. 0; trace blood; 2+ protein; 1+ glucose; trace leukocyte esterase; no ketones, nitrites, cells, or formed elements C Salicylate toxicity D Sepsis

• Respiratory alkalosis • Excessive decrease in bicarbonate (decrease of more than 2 in bicarb when only 5 drop in PCO 2) • AG Metabolic acidosis also present • Used oil of wintergreen (methyl salicylate) • Mental status changes, nausea, fever, vomiting and tinnitus

• Metformin Toxicity leads to lactic acidosis (normal lactic acid level (6 -16)) • Methanol poisoning leads to increased osmolal gap (308 -304 =4) • Sepsis unlikely based on clinical picture and absence of leukocytosis

A 41 -year-old woman is evaluated during a follow-up visit for high blood pressure. On physical examination, blood pressure is 162/100 mm Hg, which is similar to the values measured at her initial visit. Other vital signs are normal. BMI is 21. Laboratory studies are normal. Which of the following is the most appropriate next step in the management of this patient's hypertension? A Combination drug therapy B Lifestyle modifications C Single-drug therapy D Reevaluate patient in 2 weeks

• Stage 2 HTN ( SBP > 160 or DBP > 100) • Goal for this patient is 140/90 • If require reduction of SBP > 20 or DBP > 10, combination therapy is recommended • Can shorten time for needed for medication adjustment • Can increase likelihood of BP goal

An 81 -year-old man is evaluated for progressive fatigue. Nine months ago, he was diagnosed with giant cell arteritis; at that time, prednisone, omeprazole, risedronate, and vitamin D were initiated. His symptoms improved, and the prednisone was tapered. Five months ago he began to feel more fatigued. Evaluation was unremarkable other than the urinalysis, which was positive for leukocytes and leukocyte esterase. He was treated with ciprofloxacin without improvement of his symptoms. A subsequent urine culture was negative. Which of the following is the most likely diagnosis? Laboratory studies: Hemoglobin 10. 7 g/d. L (107 g/L) Leukocyte count 8700/µL (8. 7 × 109/L) (65% neutrophils, 23% lymphocytes, 11% monocytes, and 1% eosinophils) Platelet count 198, 000/µL (198 × 109/L) Blood urea nitrogen 51 mg/d. L (18. 2 mmol/L) Serum creatinine 3. 1 mg/d. L (274 µmol/L) (baseline: 1. 1 mg/d. L [97. 2 µmol/L]) Lactate dehydrogenase 80 units/L Urinalysis Specific gravity 1. 014; p. H 6. 0; trace protein; + leukocyte esterase; occasional leukocytes; rare erythrocytes; occasional hyaline casts A Acute interstitial nephritis B Acute tubular necrosis C Glomerulonephritis D Thrombotic thrombocytopenic purpura

• • Hypersensitivity to medication PPI is common Eosinophils on differential Leukocytes and possibly leukocytes casts with negative culture

• ATN presents with muddy brown casts • Can be induced by bisphonates • Giant cell arteritis affects large blood vessels, not usually small vessels of kidneys • Would expect dysmorphic erythrocytes and erythrocyte casts • TTP would see thrombocytopenia and microangiopathic hemolytic anemia

A 26 -year-old man is evaluated in the emergency department after being found on the floor in his apartment by friends who had not seen him in several days. On physical examination, the patient is somnolent and minimally responsive. Temperature is 37. 2 °C (98. 9 °F), blood pressure is 92/54 mm Hg, pulse rate is 118/min, and respiration rate is 14/min with 97% oxygen saturation on ambient air. BMI is 25. Skin is mottled and edematous on the posterior surface of the legs, buttocks, and back. Neurologic examination reveals no focal or lateralizing findings. The remainder of the examination is normal. Which of the following is the most appropriate treatment for this patient? A Hemodialysis B Intravenous mannitol C Rapid infusion of intravenous 0. 9% saline D Rapid infusion of intravenous 5% glucose Laboratory studies: Blood urea nitrogen 174 mg/d. L (62. 1 mmol/L) Calcium 7. 8 mg/d. L (2. 0 mmol/L) Creatine kinase 125, 000 units/L Serum creatinine 8. 3 mg/d. L (734 µmol/L) Electrolytes Sodium 151 meq/L (151 mmol/L) Potassium 5. 8 meq/L (5. 8 mmol/L) Chloride 121 meq/L (121 mmol/L) Bicarbonate 19 meq/L (19 mmol/L) Glucose 94 mg/d. L (5. 2 mmol/L) Phosphorus 8. 5 mg/d. L (2. 75 mmol/L) Urinalysis Specific gravity 1. 012; p. H 6. 5; 3+ blood; 1+ protein; 0 -5 erythrocytes/hpf; 1 -3 leukocytes/hpf; dark granular casts Toxicology screening Pending